Phenylalanine, one of the nine essential amino acids that the human body cannot produce on its own, is important in various physiological processes. 

This versatile compound exists in two isomers, D- and L-form, each with distinct potential health benefits. 

As a precursor to tyrosine, phenylalanine indirectly supports the production of important neurotransmitters and hormones such as dopamine, norepinephrine, epinephrine, melanin, and thyroid hormone. 

While it is vital for protein synthesis, mood regulation, and immune function, phenylalanine also requires careful consideration in certain health conditions.

For individuals with chronic kidney disease, elevated levels of phenylalanine can contribute to the progression of the condition, while those with phenylketonuria (PKU) must strictly limit their intake due to an inability to properly metabolize this amino acid.

Found naturally in high-protein foods and as a component of the artificial sweetener aspartame, phenylalanine's impact on health spans from potential benefits in pain management and skin pigmentation to risks associated with excessive consumption or specific metabolic disorders.

What is Phenylalanine? [13., 15.] 

Phenylalanine is one of the nine essential amino acids that cannot be synthesized by the human body and must be obtained through diet.

Phenylalanine exists in two isomers, the D- form and L-form. Each may have distinct benefits on human health. [5., 6.]  

Phenylalanine is a precursor to tyrosine, another important amino acid. The conversion of phenylalanine to tyrosine is catalyzed by the enzyme phenylalanine hydroxylase, which requires tetrahydrobiopterin as a cofactor.  [29.] 

Tyrosine is then converted to dopamine, norepinephrine, epinephrine, melanin, or thyroid hormone, so phenylalanine indirectly supports production of these hormones and neurotransmitters.   

Phenylalanine, along with tyrosine and tryptophan, are precursors of major uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS), which are known to contribute to the progression of chronic kidney disease (CKD). [3.]

In chronic kidney disease (CKD), there is an impairment in the conversion of phenylalanine to tyrosine. This leads to elevated phenylalanine levels and a decreased tyrosine/phenylalanine ratio in patients with kidney dysfunction. 

Daily Phenylalanine Requirements and Signs of Deficiency

The recommended daily intake of phenylalanine is generally between 9.03 and 15.9 mg/kg/day for most adults. [17.] 

However, studies show that the phenylalanine requirement for most humans is 30-40 mg/kg/day. [14.]

True phenylalanine deficiency is rare in humans consuming a normal diet. 

General protein deficiency symptoms include: [23.] 

• Muscle wasting or weakness

• Slow wound healing

• Increased risk of infections due to weakened immune system

• Fatigue and weakness

• Hair, skin, and nail problems

• Edema (swelling) due to fluid retention

• Mood changes and irritability

• Increased hunger

Health Benefits of Phenylalanine

Production of Neurotransmitters and Hormones

Phenylalanine is used to produce tyrosine, dopamine, norepinephrine, and epinephrine.  Tyrosine is also a precursor to thyroid hormone and melanin.

These compounds are crucial for various bodily functions, including mood regulation and stress response.

Mood Regulation

May help reduce symptoms of depression. Studies have shown potential mood-boosting properties. [9.] 

Pain Management

Some research suggests that phenylalalnine may act as a natural pain reliever, particularly the D-form and DL-forms of phenylalanine. [5., 6., 28.] 

Skin Pigmentation

Phenylalanine may improve skin pigmentation in vitiligo when combined with UV light therapy, particularly in combination with certain herbs including ginkgo biloba.  This may also reduce some of the psychiatric side effects seen with vitiligo. [31.]  

Phenylalanine is required to make melanin, the pigment responsible for skin color. 

Protein Synthesis

As an essential amino acid, it's crucial for the production of proteins in the body

Proteins are vital for numerous bodily functions and structures.

Immune Function

Phenylalanine has shown benefit in stimulating the innate immune system and in reducing the macrophage-driven inflammatory response. [11., 32.] 

D-phenylalanine may also inhibit biofilm formation from Staphylococcus aureus. [10.] 

Alcohol Withdrawal

May help alleviate symptoms of alcohol withdrawal when combined with other amino acids. 

A food supplement containing D-phenylalanine, L-glutamine, and L-5-hydroxytryptophan was found to alleviate alcohol withdrawal symptoms and increase CD4 lymphocyte counts in patients undergoing detoxification therapy, without significantly affecting serum cortisol levels. [12.] 

This prospective, randomized, double-blind study involved 20 patients and showed a significant decrease in psychiatric symptoms in the supplemented group compared to the placebo group over a 40-day period. [12.] 

What are the Dangers of Phenylalanine?

Phenylalanine in Chronic Kidney Disease

Research has also focused on the effects of reducing dietary aromatic amino acids like phenylalanine in chronic kidney disease. [3.] 

In one experimental setup, mice with induced kidney failure were fed different diets, including a low aromatic amino acid diet (LA-AAD). 

Results indicated that both a low protein diet (LPD) and LA-AAD significantly reduced proteinuria, kidney fibrosis, and inflammation, with the LA-AAD showing a more substantial decrease in the free fractions of p-cresyl sulfate and indoxyl sulfate compared to the LPD. [3.] 

These findings suggest that dietary restrictions on aromatic amino acids, such as phenylalanine, can confer renal benefits similar to those of protein restriction, primarily through the reduction of uremic toxins, thus offering a potential dietary strategy for managing CKD.

Phenylketonuria (PKU) [18., 21.] 

Phenylketonuria (PKU) is a rare inherited metabolic disorder characterized by a deficiency in the enzyme phenylalanine hydroxylase (PAH), which is essential for processing the amino acid phenylalanine. 

This deficiency leads to a harmful accumulation of phenylalanine in the blood, which, if untreated, causes intellectual disability and other severe health issues. 

Symptoms of PKU range from mild to severe, with the most severe form, classic PKU, leading to permanent intellectual disability, seizures, and behavioral problems if not managed early. Less severe forms may pose a lower risk of brain damage. 

PKU is typically managed through a phenylalanine-restricted diet, avoiding high-protein foods and certain artificial sweeteners. 

Newborn screening allows for early diagnosis and treatment, significantly reducing the risk of severe outcomes. Pregnant women with PKU must adhere to a strict diet to prevent developmental issues in their babies. 

PKU is inherited in an autosomal recessive pattern and affects various ethnic groups, with specific dietary and medical treatments available to manage the condition throughout life.

Sources of Phenylalanine

What Foods Have Phenylalanine?

Phenylalanine is found in various foods, particularly high-protein foods. Dietary sources of Phenylalanine include meat, fish, eggs, dairy products, soy products, nuts, and seeds.  [16.] 

Some fruits and vegetables also contain Phenylalanine, though in smaller amounts. Peas, avocado, watercress, arugula, parsley, and coriander are relatively higher in phenylalanine. [2.] 

In addition to natural food sources, Phenylalanine is available as a dietary supplement, often used to support cognitive function and mental health, immune function, and promote pain relief.

Why is Phenylalanine in Some Drinks? 

Phenylalanine is commonly found in diet sodas and other low-calorie beverages that use aspartame as a sugar substitute. 

When consumed, aspartame is broken down in the body, and one of its breakdown products is phenylalanine. 

Due to the presence of phenylalanine from aspartame, products containing this sweetener are required to carry a warning label for individuals with phenylketonuria (PKU). People with PKU need to be particularly cautious about consuming drinks containing aspartame, as they cannot properly metabolize phenylalanine .

While phenylalanine itself is an essential amino acid that the body needs, it becomes a concern primarily for individuals with PKU who must carefully manage their phenylalanine intake.

Phenylalanine Side Effects

While Phenylalanine offers numerous health benefits, it is also associated with several potential side effects, especially when consumed in excess or by individuals with certain health conditions. 

Interactions with Medications

Phenylalanine can interact with certain medications, potentially altering their effects or increasing the risk of side effects. 

Levodopa

Individuals taking medications for Parkinson's disease such as Levodopa should avoid supplementing with phenylalanine. [22.] 

Baclofen

Phenylalanine may inhibit absorption of Baclofen. [4.] 

MAOIs

Monoamine oxidase inhibitors (MAOIs) are a class of antidepressants that inhibit the breakdown of neurotransmitters like dopamine and norepinephrine. The addition of Phenylalanine can lead to excessively high levels of a compound called tyramine, resulting in severe hypertension or a hypertensive crisis. [30.] 

Side Effects of Excessive Phenylalanine Use

Excessively high levels of phenylalanine may be associated with certain side effects including constipation, nausea, heartburn, headaches, vertigo, anxiety, insomnia and rarely, hypomania. [20.] 

Impact on Individuals with Phenylketonuria (PKU)

Phenylketonuria (PKU) is a genetic disorder in which the body cannot properly metabolize phenylalanine due to a deficiency in the enzyme phenylalanine hydroxylase. 

As a result, phenylalanine accumulates in the blood, leading to toxic levels that can cause severe brain damage and intellectual disability if not managed from birth. 

For individuals with PKU, even small amounts of phenylalanine can be harmful, necessitating a strict low-Phenylalanine diet to prevent complications. 

Foods high in phenylalanine such as meat, dairy products, and certain artificial sweeteners like aspartame must be avoided. Regular monitoring of blood Phenylalanine levels is essential to manage the condition effectively.

Phenylalanine Dangers

While Phenylalanine is essential for many physiological processes, excessive intake or specific health conditions can make its consumption dangerous. 

Pregnancy and Breastfeeding

PHenylalanine is likely safe when consumed in whole foods like meat and dairy products.  However, excessive supplementation of phenylalanine is not recommended, and is strictly contraindicated in pregnant people with PKU. 

Serum levels of phenylalanine greater than 360 mmol/L are associated with an increased risk of birth defects. [25.] 

Risks for Individuals with Metabolic Disorders (PKU)

For individuals with Phenylketonuria (PKU), managing phenylalanine intake is critical to prevent serious health complications. 

PKU is a genetic disorder where the enzyme phenylalanine hydroxylase is deficient or absent, leading to an inability to metabolize Phenylalanine into tyrosine. As a result, Phenylalanine accumulates in the blood and brain, causing toxic effects. 

Individuals with PKU must adhere to a strict low-phenylalanine diet, avoiding high-protein foods such as meat, fish, eggs, dairy, and certain artificial sweeteners like aspartame. 

Failure to manage phenylalanine intake can lead to severe cognitive impairment, behavioral problems, and other health issues.

Testing Phenylalanine Levels

Test Information, Sample Collection and Preparation

Amino acids including Phenylalanine may be tested in blood or urine. Blood tests require a venipuncture, while urine samples may be collected from the comfort of home. 

Fasting is generally required prior to sample collection. It is important to consult with the ordering provider prior to sample collection to determine whether certain supplements should be avoided. 

Plasma vs. Urine Assessment of Amino Acids

Plasma amino acid testing and urine amino acid testing are both valuable diagnostic tools used to assess amino acid metabolism and provide insights into various aspects of health. However, each method offers distinct advantages. 

Plasma amino acid testing involves the analysis of amino acid levels in the bloodstream, offering real-time information about amino acid concentrations and their role in metabolic processes. 

This method provides a snapshot of amino acid status and allows clinicians to identify immediate metabolic dysregulation, amino acid deficiencies, and imbalances in metabolic pathways. 

Additionally, plasma amino acid testing enables the evaluation of amino acid levels associated with neurotransmitter synthesis, providing insights into neurotransmitter balance and cognitive health. [19.]  A plasma sample is also recommended when kidney function is compromised.

Recent food intake briefly elevates plasma levels, making fasting samples preferable. While short-term fasting doesn't deplete plasma amino acids, long-term malnutrition does. 

Despite good correlation between plasma and urine amino acids, urine samples represent recent dietary intake and metabolism, offering insight into fluctuating diets or controlled dietary changes. 

Urine samples, collected conveniently at home, are suitable for assessing controlled diets or recent dietary modifications, although results are influenced by kidney function, with biomarkers ratioed to urine creatinine.

In contrast, urine amino acid testing offers a comprehensive view of amino acid excretion and metabolic waste products.  [24.]   

While urine amino acid testing may not provide real-time information about amino acid concentrations in the bloodstream, it offers valuable insights into amino acid metabolism and renal function.

Urine amino acid testing is often used to screen for inborn errors of amino acid metabolism, although it is also used in assessing long-term metabolic health and monitoring treatment responses over time. [1.]

Interpreting Phenylalanine Test Results

Optimal Levels of Phenylalanine

Phenylalanine levels should be interpreted within the context of an individual’s full medical history, depending on the sample type used. 

One laboratory company recommends a plasma Phenylalanine level between 31.7 - 71.0

nmol/mL. [26.] 

Another laboratory company recommends a urine Phenylalanine level between 8-71 micromol/g creatinine. [27.] 

Clinical Significance of Excessive Phenylalanine Levels

Although rare, excessively high Phenylalanine levels may indicate excessive supplementation or decreased metabolism and utilization of Phenylalanine, as in PKU. 

Excessive phenylalanine levels may also be associated with unwanted side effects including gastrointestinal distress, headaches, or anxiety and insomnia.

Clinical Significance of Decreased Phenylalanine Levels

Decreased Phenylalanine levels may be associated with malnutrition or poor protein intake, or digestive insufficiency. In urine tests, low levels of amino acids such as phenylalanine may signal kidney disease. 

FAQ: Phenylalanine

Phenylalanine is an essential amino acid that plays a vital role in the body's functioning. It is important for the production of proteins and various neurotransmitters. This FAQ section addresses common questions about phenylalanine, its benefits, sources, and potential side effects.

What is Phenylalanine?

Phenylalanine is an essential amino acid that is a building block of proteins. It is necessary for the production of other important molecules such as tyrosine, epinephrine, norepinephrine, and dopamine, which are crucial for various bodily functions.

What are Phenylalanine Benefits?

Phenylalanine offers several benefits, including its role in the production of neurotransmitters that help regulate mood and mental health. It is also involved in the synthesis of proteins and the production of thyroid hormones, which are crucial for metabolic processes.

What Does Phenylalanine Do to Your Body?

Phenylalanine is converted into tyrosine in the body, which then helps produce important neurotransmitters like dopamine, norepinephrine, and epinephrine. These neurotransmitters are essential for brain function, mood regulation, and the body's stress response.

What are Phenylalanine Side Effects?

While phenylalanine is generally safe for most people when consumed in food, high doses from supplements can cause side effects such as headaches, anxiety, and nausea. 

People with the genetic disorder phenylketonuria (PKU) should avoid phenylalanine as their bodies cannot properly metabolize it, leading to harmful levels in the brain.

What are Phenylalanine Dangers?

Excessive intake of phenylalanine can lead to an imbalance of amino acids in the body and potential neurotoxicity, especially in individuals with PKU. 

It is important to monitor intake and consult a healthcare provider if considering phenylalanine supplements.

What is Phenylalanine in Drinks?

Phenylalanine is commonly found in diet sodas and other sugar-free beverages as part of the artificial sweetener aspartame. People with PKU need to be cautious of these drinks as they can contribute to harmful levels of phenylalanine.

What Foods Have Phenylalanine?

Phenylalanine is present in many high-protein foods. Common sources include meat, fish, eggs, dairy products, nuts, seeds, soy products, and certain legumes. Including these foods in your diet can help ensure you get an adequate amount of phenylalanine.

If you have any other questions about phenylalanine, feel free to reach out to a healthcare professional for personalized advice.

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